Establishment of an Adult Medaka Fatty Liver Model by Administration of a Gubra-Amylin-Nonalcoholic Steatohepatitis Diet Containing High Levels of Palmitic Acid and Fructose.

Koichi Fujisawa,Naoki Yamamoto,Shoki Okubo,Yusaku Yamada,Toshihiko Matsumoto,Keisuke Kondo,Isao Sakaida,Taro Takami,Yuto Nishimura

doi:10.3390/ijms22189931

Koichi Fujisawa, Naoki Yamamoto + Show 7 more

Open Access

https://doi.org/10.3390/ijms22189931

Copy DOI

Abstract

Among lifestyle-related diseases, fatty liver is the most common liver disease. To date, mammalian models have been used to develop methods for inhibiting fatty liver progression; however, new, more efficient models are expected. This study investigated the creation of a new model to produce fatty liver more efficiently than the high-fat diet medaka model that has been used to date. We compared the GAN (Gubra-Amylin nonalcoholic steatohepatitis) diet, which has been used in recent years to induce fatty liver in mice, and the high-fat diet (HFD). Following administration of the diets for three months, enlarged livers and pronounced fat accumulation was noted. The GAN group had large fat vacuoles and lesions, including ballooning, compared to the HFD group. The GAN group had a higher incidence of lesions. When fenofibrate was administered to the fatty liver model created via GAN administration and liver steatosis was assessed, a reduction in liver fat deposition was observed, and this model was shown to be useful in drug evaluations involving fatty liver. The medaka fatty liver model administered with GAN will be useful in future fatty liver research.

Highlights

Lifestyle factors, such as dietary habits, exercise, smoking, and alcohol consumption, greatly contribute to the onset and progression of lifestyle-related diseases, such as diabetes, obesity, hyperlipidemia, and hypertension
The liver weight (Figure 1C,D), and liver–weight ratio (Figure 1E,F) of the control group were similar those of the normal diet group; increases were observed in the high-fat diet (HFD) and GAN groups
Diet, obesity, steatosis, lobular inflammation, and hepatocellular ballooning occur, and it is effective in creating a fatty liver model [3]

Summary

Introduction

Lifestyle factors, such as dietary habits, exercise, smoking, and alcohol consumption, greatly contribute to the onset and progression of lifestyle-related diseases, such as diabetes, obesity, hyperlipidemia, and hypertension. Among the lifestyle-related diseases, fatty liver caused by over nutrition is the most common liver disease, with the number of affected patients increasing continuously. Fatty liver disease is the collective name for liver damage caused by fat deposits in hepatocytes. When no clear history of alcohol use exists, it is referred to as nonalcoholic fatty liver disease (NAFLD). NAFLD is classified into simple fatty liver, which has a good prognosis, and nonalcoholic steatohepatitis, which has been reported to progress over time to cirrhosis, and liver cancer [1]. To develop methods of inhibiting fatty liver progression, mice have been used; new, more efficient models are required [2]

Objectives

Methods

Results

Conclusion